Obesity is a medical condition of abnormal fat accumulation caused by the imbalance between energy intake and expenditure. Obesity is considered as a serious public health problem worldwide. The prevalence of obesity is increasing noticeably in Korea as well owing to various factors such as rapid industrial growth, westernization of dietary patterns, and insufficient physical activity. In addition to its own risk, obesity increases the likelihood of hyperinsulinemia, arteriosclerosis, cardiovascular diseases, certain types of cancer, and diabetes, making it more serious (Nature, 404(6778): 635-643, 2000, Obes. Rev. 12(1): 1-13, 2011).
Adipose tissue is an energy-storing organ. Excessive energy intake is a direct cause of obesity because it accelerates adipocyte differentiation and increases fat storage in the human body.
Adipocyte differentiation refers to the process in which preadipocytes proliferate and differentiate into mature adipocytes. During this process, lipogenesis-related proteins FAS (fatty acid synthase) and ACC (acetyl-CoA carboxylase) are expressed under the control of transcription factors such as PPARγ (peroxisome proliferator-activated receptor gamma), C/EBPs (CCAAT/enhancer binding proteins), and SREBP1c (sterol regulatory element binding protein 1c). These transcription factors are induced at different time points during the process, and interact with each other to regulate adipocyte-specific gene expression and to induce adipocyte differentiation (J. Agri. Food Chem. 60(4): 1094-1101, 2012, Nutr. Metab. 6(20): 1-20 2009).
Differentiated adipocytes store triglycerides in the cytoplasm. AMPK (AMP-activated protein kinase) activation stimulates signaling pathways which increase energy production involving glucose transport and fatty acid oxidation. Subsequently generated energy is consumed during physical exercise and thermogenesis. Thermogenesis is mediated by UCPs (uncoupling proteins) present in the mitochondrial inner membrane in adipose tissues and muscles, regulating energy homeostasis in the body. Expression of UCPs is known to be regulated by transcription factors PPAR and PGC-1 (peroxisome proliferator-activated receptor coactivator-1) (Pediatr. Cardiol. 32(3): 323-328, 2011).
Among the representative anti-obesity drugs developed so far, Reductil™ (Abbott, USA), which suppresses the appetite, and Xenical™ (Roche, Swiss), which blocks fat absorption, are currently used clinically for the treatment of obesity. However, therapeutic effects of these drugs are not sufficiently sustainable because of side-effects associated with cardiovascular and respiratory conditions, hypertension, and insomnia (Phytochem. 71: 1625-1641, 2010). Therefore, research is actively underway to develop anti-obesity drug substance from natural sources having a good safety profile with less adverse side-effects such as plant extracts rather than synthetic chemicals.